Modelling how ribavirin improves interferon response rates in hepatitis C virus infection

Nearly 200 million individuals worldwide are currently infected with hepatitis C virus (HCV). Combination therapy with pegylated interferon and ribavirin, the latest treatment for HCV infection, elicits long-term responses in only about 50% of patients treated. No effective alternative treatments ex...

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Bibliographic Details
Published in:Nature 2004-12, Vol.432 (7019), p.922-924
Main Authors: Perelson, Alan S, Dixit, Narendra M, Layden-Almer, Jennifer E, Layden, Thomas J
Format: Article
Language:English
Subjects:
Biological and medical sciences
Dose-Response Relationship, Drug
Drug Therapy, Combination
Hepacivirus - drug effects
Hepacivirus - genetics
Hepacivirus - physiology
Hepatitis C - drug therapy
Hepatitis C - virology
Hepatitis C virus
Human viral diseases
Humanities and Social Sciences
Humans
Infectious diseases
Interferons - pharmacology
Interferons - therapeutic use
letter
Medical sciences
Models, Biological
multidisciplinary
Ribavirin - pharmacology
Ribavirin - therapeutic use
RNA, Viral - genetics
RNA, Viral - metabolism
Science
Science (multidisciplinary)
Viral diseases
Viral hepatitis
Viral Load
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Summary:Nearly 200 million individuals worldwide are currently infected with hepatitis C virus (HCV). Combination therapy with pegylated interferon and ribavirin, the latest treatment for HCV infection, elicits long-term responses in only about 50% of patients treated. No effective alternative treatments exist for non-responders. Consequently, significant efforts are continuing to maximize response to combination therapy. However, rational therapy optimization is precluded by the poor understanding of the mechanism(s) of ribavirin action against HCV. Ribavirin alone induces either a transient early decline or no decrease in HCV viral load, but in combination with interferon it significantly improves long-term response rates. Here we present a model of HCV dynamics in which, on the basis of growing evidence, we assume that ribavirin decreases HCV infectivity in an infected individual in a dose-dependent manner. The model quantitatively predicts long-term response rates to interferon monotherapy and combination therapy, fits observed patterns of HCV RNA decline in patients undergoing therapy, reconciles conflicting observations of the influence of ribavirin on HCV RNA decline, provides key insights into the mechanism of ribavirin action against HCV, and establishes a framework for rational therapy optimization.
ISSN:0028-0836
1476-4687
DOI:10.1038/nature03153